Three Part Question

In [children with tonsillitis], [how long should antibiotics be given]? [outcome]

Clinical Scenario

A 3 year old boy was brought to the ED because of a fever, sore throat and an inflamed and tender tonsils. A diagnosis of tonsillitis was made. What course of antibiotics should be prescribed to the child? Which is more effective, a short-course or long-course antibiotic?

501 children (2 - 12 years old) were randomized to receive either Azithromycin 10mg/kg/day once daily for 3 days or Azithromycin 20mg/kg/day once daily for 3 days or penicillin V 45 mg/kg/day three times daily for 10 days

Prospective, randomized clinical trial

Microbiological response on Day 14

AZM 10 mg/kg significantly less (P= 0.0001) than the other two groups. 90% CI for the mean difference between AZM 20 mg/kg and penicillin V (4.1% - 15.9%)

One study arm was not blinded due to the nature of the dosage of medication.
P values for baseline characteristics were not calculated

D.Adam et al6/7/2011Germany

1-18 year olds with established diagnosis of group A streptococcal tonsillopharyngitis clinically and microbilogically.

phase IV, randomized, open label, comparative, multicentre study

Clinical response at end of treatment (7-9 days post-treatment)

Cefuroxime axetil (97.2%) vs penicillin V (93.3%); P=0.001

This study is an arm or a larger study assessing several agents for the eradication of GABHS.
A degree of subjectivity in the exclusion criteria.
Blinding of patients and investigators were not possible.
Study power calculation were done using a chi test which resulted in 1590patients in the penicillin arm vs 530 patients in the cefuroxime axetil arm.
Discussion possibly bias.

Microbiological response at end of treatment (7-9 days post-treatment)

Cefuroxime axetil (90.0%) vs penicillin V (84.1%); P=0.001

M.Falagas et al.6/7/2011USA

Eleven RCTs comparing short-course vs long-course treatment (5 with penicillin V, 4 with oral cephalosporins, 1 with intramuscular ceftriaxone, and 1 with clindamycin; 6 of the 11 were open label) were included. Age groups included 1-80 year olds.

20 RCTs were included in this review which investigated a total of 13,102 cases of
GABHS throat infections (tonsillitis, pharyngitis, tonsillopharyngitis) in children and young adults ranging from 1 to 18 year olds (except one study that included adults up to 25 years old). All studies only included patients who were diagnosed with GABHS by rapid antigen detection test or throat culture. The selected papers compared a short-course of several different antibiotics (azithromycin (n=6), cefuroxime (n=3), erythromycin (n = 2), clarithromycin (n = 3), cefixime (n =1), amoxacillin (n = 1), amoxacillin/clavulanate (n = 2), penicillin V
(n =1), cefprozil (n = 1), cefpodoxime (n = 1), jasomycin (n = 1),
cefdinir (n = 1), ceftibutin (n = 1) and loracarbef (n = 1)) against the standard treatment of 10 day penicillin V.

Systematic Review

Time to fever resolution

Only reported in two studies. Both studies favored the short duration group. In the first study, the short duration group had a mean duration of fever of 2.04 days compared with 2.38 days in the standard duration group, while in the second study the durations were 2.82 days and 3.1 days, respectively (MD -0.30, 95% CI -0.45 to -0.14).

Time to sore throat resolution

Only reported in one study. Mean duration of sore throat was 2.19 days (SD 0.81) in the short duration treatment group and 2.69 days (SD 1.13) in the standard duration treatment group (MD -0.50, 95% CI -0.78 to -0.22).

Early clinical treatment failure (persistence in symptoms within the first 2 weeks of treatment completion)

19 study reported on this outcome. The short duration treatment group showed a lower risk of early clinical treatment failure (OR 0.80, 95% CI 0.67 to 0.94).

Thirteen studies assessed the risk of late clinical recurrence. The risk of late clinical recurrence was not statistically different between short duration and standard duration groups (OR 0.95, 95% CI 0.83 to 1.08).

Early bacteriological treatment failure (persistence of the same strain of GABHS within the first 2 weeks after completion of treatment)

All included studies assessed this outcome. There was no significant difference in the risk of early bacteriological treatment failure between short duration and standard duration groups (OR 1.08, 95% CI 0.97 to 1.20).

Late bacteriological recurrance (recurrance of thesame GABHS strain, after initial resolution, beyond the first 2 weeks after completion of treatment)

All studies assessed this outcome. The risk of late bacteriological recurrence was significantly worse in the short duration treatment groups (OR 1.31, 95% CI 1.16 to 1.48). However, when eliminating the studies of low-dose azithromycin (10mg/kg), which performedmuch worse than other short duration regimens (OR 3.62, 95% CI 2.66 to 4.92), the two treatment groups were no longer statistically different (OR 1.06, 95% CI 0.92 to 1.22).

Comment(s)

These papers are comparing short-courses of different antibiotics with the standard treatment of tonsillitis which is 10 days of penicillin V. More evidince exists comparing different antibiotics with the current gold standard but there aren't many recent evidence to compare between a shorter course of penicillin with the standard 10 day course.

Clinical Bottom Line

Shorter courses improves compliance and in most cases resolves symptoms and eradicates the organism. However, more often than not, it's not as effective as 10 day penicillin V course in terms of long term effects and recurrance rates.